Journal article
Ectodermal Organ Development Is Regulated by amicroRNA-26b-Lef-1-WntSignaling Axis
Frontiers in physiology, Vol.11, 780
07/14/2020
DOI: 10.3389/fphys.2020.00780
PMCID: PMC7372039
PMID: 32760291
Abstract
The developmental role ofLef-1in ectodermal organs has been characterized usingLef-1murine knockout models. We generated aLef-1conditional over-expression (COEL) mouse to determine the role ofLef-1expression in epithelial structures at later stages of development after endogenous expression switches to the mesenchyme.Lef-1over expression (OE) in the oral epithelium creates a new dental epithelial stem cell niche that significantly increases incisor growth. These data indicate thatLef-1expression is switched off in the dental epithelial at early stages to maintain the stem cell niche and regulate incisor growth. Bioinformatics analyses indicated thatmiR-26bexpression increased coinciding with decreasedLef-1expression in the dental epithelium. We generated a murine model over-expressingmiR-26bthat targets endogenousLef-1expression andLef-1-related developmental mechanisms.miR-26bOE mice have ectodermal organ defects including a lack of incisors, molars, and hair similar to theLef-1null mice.miR-26bOE rescues theLef-1OE phenotype demonstrating a critical genetic and developmental role formiR-26bin the temporal and spatial expression ofLef-1in epithelial tissues.Lef-1expression regulates Wnt signaling and Wnt target genes as well as cell proliferation mechanisms, whilemiR-26bOE reduced the levels of Wnt target gene expression. The extra stem cell compartment in theCOELmice expressedLef-1suggesting thatLef-1is a stem cell factor, which was absent in themiR-26b OE/COELrescue mice. This is the first demonstration of a microRNA OE mouse model that has ectodermal organ defects. These findings demonstrate that the levels ofLef-1are critical for development and establish a role formiR-26bin the regulation of ectodermal organ development through the control ofLef-1expression and an endogenous stem cell niche.
Details
- Title: Subtitle
- Ectodermal Organ Development Is Regulated by amicroRNA-26b-Lef-1-WntSignaling Axis
- Creators
- Steve Eliason - University of IowaThad Sharp - University of IowaMason Sweat - University of IowaYan Y. Sweat - University of IowaBrad A. Amendt - Iowa Institute for Oral Health Research, The University of Iowa, Iowa City, IA, United States.
- Resource Type
- Journal article
- Publication Details
- Frontiers in physiology, Vol.11, 780
- DOI
- 10.3389/fphys.2020.00780
- PMID
- 32760291
- PMCID
- PMC7372039
- NLM abbreviation
- Front Physiol
- ISSN
- 1664-042X
- eISSN
- 1664-042X
- Publisher
- Frontiers Media Sa
- Number of pages
- 14
- Grant note
- 5T90DE023520-07; R43DE027569; R01DE026433; R03EB025873; R21DE025328 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 07/14/2020
- Academic Unit
- Orthodontics; Anatomy and Cell Biology; Craniofacial Anomalies Research Center; Dental Research
- Record Identifier
- 9984284329102771
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